L-carnitine inhibits hypoglycemia-induced brain damage in the rat
L-carnitine inhibits hypoglycemia-induced brain damage in the rat
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DOI：
10.1016/j.brainres.2005.06.062
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发表时间：
2005-08-16
期刊：
影响因子：
2.9
通讯作者：
Inoue, M
中科院分区：
文献类型：
--
作者：
Hino, K;Nishikawa, M;Inoue, M
低血糖有时发生在接受过量胰岛素的糖尿病患者中。已知重度低血糖会诱导线粒体肿胀，随后导致脑中神经元死亡。由于L-肉碱有效地保护线粒体功能在各种细胞在体外和体内，我们研究了其对低血糖损伤诱导的雄性Wistar大鼠神经元损伤的影响。动物给予含L-肉毒碱的水（0.1%）1周，然后接受胰岛素（20 U/kg，i. p.）诱发低血糖虽然L-肉毒碱不影响发生低血糖休克的动物的死亡率，但通过Morris水迷宫测试评估，它改善了存活动物的认知功能。左旋卡尼汀能有效地抑制海马中氧化型谷胱甘肽的增加和线粒体功能障碍，防止神经元损伤。左旋卡尼汀还能抑制缺糖培养的海马神经元细胞线粒体膜电位的降低和活性氧的产生。这些结果表明，L-肉毒碱防止低血糖引起的海马神经元损伤，大概是通过保存线粒体功能。因此，左旋肉碱可能对胰岛素过量引起的低血糖患者具有治疗潜力。(c)2005 Elsevier B. V.保留所有权利。
Hypoglycemia sometimes occurs in patients with diabetes mellitus who receive excessive doses of insulin. Severe hypoglycemia has been known to induce mitochondrial swelling followed by neuronal death in the brain. Since L-carnitine effectively preserves mitochondrial function in various cells both in vitro and in vivo, we investigated its effects on the neuronal damage induced by hypoglycemic insult in male Wistar rats. Animals were given L-carnitine-containing water (0.1%) for 1 week and then received insulin (20 U/kg, i.p.) to induce hypoglycemia. Although L-carnitine did not affect the mortality of animals that developed hypoglycemic shock, it improved the cognitive function of the survived animals as assessed by the Morris water-maze test. L-Carnitine effectively inhibited the increase in oxidized glutathione and mitochondrial dysfunction in the hippocampus and prevented neuronal injury. L-Carnitine also inhibited the decrease in mitochondrial membrane potential and the generation of reactive oxygen species in hippocampal neuroral cells cultured in glucose-deprived medium. These results suggest that L-carnitine prevents hypoglycemia-induced neuronal damage in the hippocampus, presumably by preserving mitochondrial functions. Thus, L-carnitine may have therapeutic potential in patients with hypoglycemia induced by insulin overdose. (c) 2005 Elsevier B.V. All rights reserved.